We plan to study the factors promoting progressive cartilage destruction in animal models of osteoarthrosis in order to understand the pathophysiology of this condition. The effectiveness of these models has been established by previous experimentation. The joint tissues are studied biochemically, metabolically, and biomechanically. Since the pathology of osteoarthrosis involves destruction of the articular cartilage and the remodeling of the bone adjacent to the joints, we must use in vivo preparations because osteoarthrosis mainly affects mature, older individuals and its development involves an inter-relationship between a variety of tissues, organ cultures utilizing fetal materials are inappropriate. This study, involving collaborative biochemical, biomechanical, anatomical, pathological, and clinical analyses of these models, should provide a better understanding of osteoarthrosis with the hope that the process can some day be halted and reversed. We propose utilizing poorly-protected-against repetitive impulsive loading of a physiologically reasonable amount to create osteoarthrosis in the right knees of rabbits. The left knee is used as a control. We want to establish the threshold levels at which articular cartilage is mechanically injured, the nature of the load which is most deleterious, and the mechanical factors responsible for progression of the joint deterioration. We will first predict the most deleterious force analytically by finite element analysis and test that hypothesis experimentally. We will also utilize stiffening, caused by remodeling of a local area of subchondral bone overlying an implanted plug just under the knee joint of a sheep to study the relationship of bone stiffening and progressive cartilage deterioration. Finite element analysis reveals that such remodeling achieved does increase the stress in the deep layers of the overlying cartilage. We plan to study this in long- and short-term animals to delineate the progression of changes. Experimental results coupled with an expansion of analytical understanding should help define the important mechanical parameters causing joint deterioration in osteoarthrosis.